Crop dusting.
Top Line: PD-L1 isn’t just on the surface of tumor cells.
The Study: Melanoma has taught us some incredibly interesting stuff about how tumors interact with and modulate the immune system. You probably know that melanoma likes to evade immune surveillance by expressing PD-L1 on its surface, which suppresses T-cell activation. If you don’t, you need to do 2017 over again. What’s new here is the discovery that melanoma cells actually release extracellular vesicles (exosomes) coated in PD-L1. That’s right, not only is the cell covered in immune-suppressive PD-L1, it releases clouds of extracellular PD-L1 to essentially “crop dust” the tumor microenvironment. The level of exosomal PD-L1 also provided two important pieces of information. High levels of pre-treatment PD-L1 were associated with immune exhaustion and poor response to therapy. However, an uptick in exosomal PD-L1 during immunotherapy appeared to indicate successful anti-tumor immune activation. It basically signifies the tumor trying to overwhelm PD-1 axis blockade. Fortunately, immunotherapy drugs can often overcome even this negative feedback loop of exosomal PD-L1 expression.
Bottom Line: Melanoma uses not only cell surface PD-L1 (and PD-1) but also exosomes coated in PD-L1 to suppress immune activity. | Chen, Nature 2018
The Study: Melanoma has taught us some incredibly interesting stuff about how tumors interact with and modulate the immune system. You probably know that melanoma likes to evade immune surveillance by expressing PD-L1 on its surface, which suppresses T-cell activation. If you don’t, you need to do 2017 over again. What’s new here is the discovery that melanoma cells actually release extracellular vesicles (exosomes) coated in PD-L1. That’s right, not only is the cell covered in immune-suppressive PD-L1, it releases clouds of extracellular PD-L1 to essentially “crop dust” the tumor microenvironment. The level of exosomal PD-L1 also provided two important pieces of information. High levels of pre-treatment PD-L1 were associated with immune exhaustion and poor response to therapy. However, an uptick in exosomal PD-L1 during immunotherapy appeared to indicate successful anti-tumor immune activation. It basically signifies the tumor trying to overwhelm PD-1 axis blockade. Fortunately, immunotherapy drugs can often overcome even this negative feedback loop of exosomal PD-L1 expression.
Bottom Line: Melanoma uses not only cell surface PD-L1 (and PD-1) but also exosomes coated in PD-L1 to suppress immune activity. | Chen, Nature 2018
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